NEUROLOGIC PERSPECTIVES OF CRIGLER-NAJJAR-SYNDROME TYPE-I

Limited information exists on the neurologic sequelae of Crigler-Najja r syndrome type I despite this being the major morbidity of this rare autosomal recessive disorder of bilirubin conjugation that results in chronic unconjugated hyperbilirubinemia. Two patients with identical u nderlying genetic mutations resulting in Crigler-Najjar syndrome type I were assessed from a neurodevelopmental perspective in late childhoo d using age appropriate standardized measures. In addition, the Englis h language literature of case reports and series describing the outcom es of patients with this disorder was reviewed (descriptive meta-analy sis) and summarized with particular reference to neurologic symptomato logy, pattern of neurologic disability, age of onset of symptoms, and therapeutic interventions. Despite radically different therapeutic int erventions, our two patients did not differ in outcome measures. Revie w of the literature reveals distinct, often age-related, patterns of n eurologic sequelae reflecting injury to basal ganglia, cerebellar, and likely hippocampal structures. Definitive prevention of the neurologi c sequelae that often occur within the context of Crigler-Najjar syndr ome type I requires that curative treatment (hepatic transplantation, presently, and gene therapy in the future) be applied prior to the pos sible onset of neurologic symptoms in adolescence.